Efficacy and Safety Study of BERIPLEX® P/N (Kcentra) Compared With Plasma in Patients With Acute Major Bleeding Caused by Anticoagulant Therapy

NCT00708435 | Completed Phase 3 Results

• 3 other identifiers: BE1116_300214622007-007861-19
• Study Type: interventional
• Target: 216
• Locations: 6 countries
• Sites: 69

Brief Summary

The purpose of this study is to evaluate efficacy, safety and tolerance of BERIPLEX® P/N (Kcentra) compared with plasma in regard to rapid reversal of coagulopathy induced by coumarin derivatives in subjects who require immediate correction of INR (International Normalized Ratio)and to stop an acute major bleeding.

Conditions

Blood Coagulation Disorders; Acute Major Bleeding

Keywords

Anticoagulant reversal; Prothrombin; Complex; Concentrate; Coagulopathy; induced by; coumarin; derivatives; Kcentra

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Achieving Hemostatic Efficacy of Stopping an Ongoing Major Bleed

  Hemostatic efficacy was determined by a blinded independent board as excellent, good, or poor/none, based on prespecified definitions. Assessments of visible or non-visible musculoskeletal bleeding were made at 1 and 4 hours after the end of infusion. Hemostatic efficacy was the binary endpoint of effective or non-effective hemostasis, where 'effective' was a hemostatic efficacy rating of "excellent" or "good," and 'non-effective' was a hemostatic efficacy rating of "poor/none".

  At 1 and 4 hours after the end of infusion

• Percentage of Participants Who Had a Rapid Decrease of the International Normalized Ratio (INR)

  A rapid decrease of the international normalized ratio (INR) was defined as an INR ≤ 1.3 at 30 minutes after the end of the infusion. The INR is a standard way to describe the time it takes for blood to clot; an INR range of 0.8 to 1.2 is considered normal for a healthy person who is not using oral anticoagulant therapy.

  30 minutes after end of infusion

Secondary Outcomes (9)

• Percentage of Participants Who Had Hemostatic Efficacy for Visible or Non-visible Musculoskeletal Bleeding

  At 3 and 6 hours after the start of infusion

• Incremental in Vivo Recovery (IVR) (Response) of Factors II, VII, IX, and X, Protein C, and Protein S for Beriplex

  Before infusion and up to 3 h after the start of infusion

• Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S

  From preinfusion until 24 h after the start of infusion

• Percentage of Participants With INR Correction at Various Times After the Start of Infusion

  From the start of infusion until INR correction; calculated at 0.5, 1, 3, 6, 12, and 24 h after the start of infusion.

• Percentage of Participants With INR Correction at Various Times After Randomization

  From randomization until INR correction; calculated at 2.5, 3, 5, 8, 14, and 26 h after randomization.

Study Arms (2)

Beriplex® P/N

EXPERIMENTAL

Biological: Beriplex® P/N (Kcentra)

Fresh frozen plasma

ACTIVE COMPARATOR

Biological: Fresh frozen plasma

Interventions

Beriplex® P/N (Kcentra) BIOLOGICAL

Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body weight

Also known as: Kcentra

Beriplex® P/N

Fresh frozen plasma BIOLOGICAL

Intravenous Infusion, dosage depending on baseline INR and body weight

Fresh frozen plasma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects ≥ 18 years
• Subjects who have received oral vitamin K-antagonist therapy
• Subjects who have acute major bleeding, defined as one of the following: life-threatening or potentially life-threatening, acute bleeding associated with a fall in hemoglobin (Hb) level ≥ 2g/dL, bleeding requiring blood product transfusion
• INR ≥ 2 within 3 hours before start of study treatment
• Informed consent has been obtained

You may not qualify if:

• Expected survival of less than 3 days, or expected surgery in less than 1 day
• Acute trauma for which reversal of vitamin K antagonists alone would not be expected to control the acute bleeding event
• Use of unfractionated or low molecular weight heparin use from 24 hours prior to enrollment or expected need within 24 hours after start of infusion
• For patients with ICH: Glasgow coma score (GCS) \< 7; intracerebral hematoma volume \> 30cc as assessed by ABC/21; for subdural hematomas: maximum thickness ≥ 10 mm, midline shift ≥ 5 mm; for subarachnoid hemorrhage: any evidence of hydrocephalus; infratentorial ICH location; epidural hematomas; intraventricular extension of hemorrhage; modified Rankin score (mRS) of \>3 prior to ICH
• History of thrombotic event, myocardial infarction, disseminated intravascular coagulation, cerebral vascular accident, transient ischemic attack, unstable angina pectoris, or severe peripheral vascular disease within 3 months of enrollment
• Known history of antiphospholipid antibody syndrome or lupus anticoagulant antibodies
• Suspected or confirmed sepsis at time of enrollment
• Large blood vessel rupture (e.g. in advanced cancer patient)
• Pre-existing progressive fatal disease with a life expectancy of less than 2 months
• Known inhibitors to coagulation factors II, VII, IX, or X; or hereditary protein C or protein S deficiency; or heparin-induced, type II thrombocytopenia
• Presence or history of hypersensitivity to components of the study medication
• Pregnant or breast-feeding women

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (69)

Study Site

Birmingham, Alabama, 35248-3280, United States

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Los Angeles, California, 90033, United States

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San Franciso, California, 94115, United States

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Newark, Delaware, 19718, United States

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Orlando, Florida, 32806, United States

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Tampa, Florida, 33606, United States

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Chicago, Illinois, 60612, United States

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Oak Park, Illinois, 60302, United States

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Hazard, Kentucky, 41701, United States

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Baltimore, Maryland, 21201, United States

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Baltimore, Maryland, 21205, United States

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Boston, Massachusetts, 02114, United States

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Worchester, Massachusetts, 01655, United States

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Ann Arbor, Michigan, 48106, United States

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Royal Oak, Michigan, 48073, United States

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Duluth, Minnesota, 55805, United States

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Minneapolis, Minnesota, 55114, United States

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Jackson, Mississippi, 39216, United States

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St Louis, Missouri, 63110, United States

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Albuquerque, New Mexico, 87131, United States

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Albany, New York, 12208, United States

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Johnson City, New York, 13790, United States

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New York, New York, 10003, United States

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New York, New York, 10029, United States

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New York, New York, 10032, United States

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Rochester, New York, 14642, United States

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Staten Island, New York, 10305, United States

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Durham, North Carolina, 27710, United States

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Allentown, Pennsylvania, 18103, United States

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Hershey, Pennsylvania, 17033, United States

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Philadelphia, Pennsylvania, 19107, United States

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Philadelphia, Pennsylvania, 19140, United States

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West Reading, Pennsylvania, 19611, United States

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Austin, Texas, 78701, United States

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El Paso, Texas, 79905, United States

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Houston, Texas, 77030, United States

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Houston, Texas, 77030, United States

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Temple, Texas, 76508, United States

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Salt Lake City, Utah, 84132, United States

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Charlottesville, Virginia, 22908, United States

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Richmond, Virginia, 23298, United States

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Minsk, Belarus

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Minsk, Belarus

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Pleven, Bulgaria

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Plovdiv, Bulgaria

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Rousse, Bulgaria

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Sofia, Bulgaria

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Sofia, Bulgaria

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Study Site 3

Sofia, Bulgaria

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Sofia, Bulgaria

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Brasov, Romania

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Bucharest, Romania

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Bucharest, Romania

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Bucharest, Romania

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Cluj-Napoca, Romania

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Timișoara, Romania

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Arkhangelsk, Russia

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Barnaul, Russia

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Barnaul, Russia

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Kazan', Russia

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Kemerovo, 650002, Russia

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Moscow, Russia

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Moscow, Russia

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Nizhny Novgorod, Russia

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Nizhny Novgorod, Russia

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Saint Petersburg, Russia

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Saint Petersburg, Russia

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Kharkiv, Ukraine

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Vinnytsa, Ukraine

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Related Publications (1)

• Sarode R, Milling TJ Jr, Refaai MA, Mangione A, Schneider A, Durn BL, Goldstein JN. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation. 2013 Sep 10;128(11):1234-43. doi: 10.1161/CIRCULATIONAHA.113.002283. Epub 2013 Aug 9.

  PMID: 23935011 RESULT

MeSH Terms

Conditions

Blood Coagulation Disorders; Hemostatic Disorders

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders

Results Point of Contact

• Title: Clinical Trial Disclosure Manager
• Organization: CSL Behring

clinicaltrials@cslbehring.com

Use email contact

Study Officials

• Program Director, Clinical R&D

  CSL Behring

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2008
• First Posted: July 2, 2008
• Study Start: June 1, 2008
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: February 3, 2014
• Results First Posted: August 13, 2013

Record last verified: 2013-09

Locations

RU (11); BU (7); US (41); BE (2); RO (6); UA (2)